Synthesis of 12-hetaryl-9,9-dimethyl-7,8,9,10-tetrahydrobenzo[a]acridin- 11(12H)-ones

Article abstract of DOI:10.1134/S107042801406013X

Three-component condensation of naphthalen-2-amine with 5-arylfuran(thiophene, N-methylpyrrole)-2-carbaldehyde and 5,5- dimethylcyclohexane-1,3-dione, as well as condensation of N-[(5- arylfuran(thiophen)-2-ylmethylidene]naphthalen-2-amine with 5,5- dimethylcyclohexane-1,3-dione gave the corresponding 12-[5-arylfuran(thiophen, N-methylpyrrol)-2-yl]-7,8,9,10-tetradrobenzo[a]acridin-11(12H)-ones.

Full text of DOI:10.1134/S107042801406013X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 6, pp. 833–839. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © N.G. Kozlov, Yu.D. Zhikharko, R.Z. Lytvyn, Yu.I. Gorak, E.D. Skakovskii, A.V. Baranovskii, L.I. Basalaeva, M.D. Obushak, 2014,
published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 6, pp. 850–856.
Synthesis of 12-Hetaryl-9,9-dimethyl-7,8,9,10-tetrahydro-
benzo[a]acridin-11(12H)-ones
N. G. Kozlova, Yu. D. Zhikharkoa, R. Z. Lytvynb, Yu. I. Gorakb, E. D. Skakovskiia,
A. V. Baranovskiic, L. I. Basalaevaa, and M. D. Obushakb
a Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: loc@ifoch.bas-net.by
b Ivan Franko National University of Lviv, Universytetska ul. 1, Lviv, 79000 Ukraine
c Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus
Received October 25, 2013
Abstract—Three-component condensation of naphthalen-2-amine with 5-arylfuran(thiophene, N-methyl-
pyrrole)-2-carbaldehyde and 5,5-dimethylcyclohexane-1,3-dione, as well as condensation of N-[(5-arylfuran-
(thiophen)-2-ylmethylidene]naphthalen-2-amine with 5,5-dimethylcyclohexane-1,3-dione gave the correspond-
ing 12-[5-arylfuran(thiophen, N-methylpyrrol)-2-yl]-7,8,9,10-tetradrobenzo[a]acridin-11(12H)-ones.
DOI: 10.1134/S107042801406013X
Organic compounds possessing an acridine frag-
ment exhibit high biological activity. There are pub-
lished data [1–3] on the synthesis of acridine-based
labeled conjugates with drugs, peptides, proteins, and
nucleic acids and antitumor and DNA-binding agents.
Blache et al. [4] reported that modified acridine deriv-
atives having a carbonyl group (alkaloid floxacrine
analogs) show a higher antibacterial activity than those
lacking carbonyl group.
Dihydroacridine derivatives are complex polynu-
clear aza heterocyclic systems; therefore, development
of simple and efficient methods for the synthesis of
such compounds is an important problem of pharma-
ceutics. The most interesting are those reactions which
ensure preparation of maximally functionalized hetero-
cyclic compounds in a minimum number of steps.
Three-component reaction of aromatic amines with al-
dehydes and CH acids provides a convenient one-step
procedure for the synthesis of polyfunctionalized poly-
nuclear heterocyclic systems. Following this approach,
we previously synthesized benzo[a]- and benzo[c]-
acridinone derivatives [5, 6].
an equimolar mixture of Schiff base IIIa–IIIh and
5,5-dimethylcyclohexane-1,3-dione (dimedone) in
boiling ethanol for 50–60 min and (2) by heating
an equimolar mixture of naphthalen-2-amine (I), het-
erocyclic aldehyde IIa–IIk, and dimedone in boiling
ethanol for 2–4 h. As a rule, crystalline products were
isolated (Scheme 1).
Schiff bases IIIa–IIIh were prepared by reaction of
naphthalen-2-amine (I) with 5-arylfuran(or thiophene)-
2-carbaldehydes IIa–IIh in alcoholic solution on heat-
ing for 30–50 min. Compounds IIIa–IIIh were isolat-
ed as individual substances, so that we were able to use
them in the above transformation. No individual Schiff
bases were isolated in the reactions with 5-aryl-1-
methyl-1H-pyrrole-2-carbaldehydes IIi–IIk, and the
corresponding benzo[a]acridine derivatives Vi–Vk
were obtained only by three-component condensation
of amine I with aldehydes IIi–IIk, and dimedone (IV).
Previously unknown compounds Va–Vk were
formed in 40–85% yield. Due to high reactivity of the
β-dicarbonyl component, no addition of acid catalyst
was necessary. The cyclic structure of diketone IV
makes it possible to introduce a carbonyl group into
the fused heterocyclic structure simultaneously with
generation of partly hydrogenated benzo[a]acridine
fragment.
In the present article we report on a selective syn-
thesis of 12-[5-arylfuran(thiophene, N-methylpyrrol)-
2-yl]-9,9-dimethyl-7,8,9,10-tetrahydrobenzo[a]acridin-
11(12H)-ones Va–Vk in two ways: (1) by heating
833

KOZLOV et al.
Scheme 1.
CHO
834
NH2
N
X
X
+
R
R
I
IIa–IIk
IIIa–IIIk
O
H
N
X
X
Me
Me
R
R
O
O
O
O
O
–I
Me
Me
Me
Me
A
B
3
4
2
1
4a
4'
3'
6''
5''
5
6
12b
5'
1''
12a
2'
1'
4''
I
6a
X
X
12
R
R
2''
3''
H2N
O
11a
O
HN
O
11
7a
8
10
9
Me
Me
Me
Me
Va–Vk
C
X = O, R = 4-O2N (a), 4-Br (b), 2-F3C (c), 4-H2NSO2 (d), 2-O2N-4-MeO (e), 2-Br-4-Me (f); X = S, R = 4-O2N (g), 3-O2N (h);
X = NMe, R = 4-Br (i), 2-Br (j), 2-Cl (k).
In keeping with the proposed reaction scheme
(Scheme 1), Schiff base III takes up dimedone mole-
cule to form unstable intermediate A which then de-
composes into arylmethylidene diketone B and initial
naphthalen-2-amine (I). Addition of the latter (through
the α-carbon atom with respect to the amino group,
which is characterized by the highest electron density)
to the exocyclic double bond of B leads to intermediate
C which undergoes heterocyclization with elimination
of water to afford final product V.
The yield of the final products depends on the
nature of the heterocyclic aldehyde component. The
best yields of benzo[a]acridinones (51–85%) were ob-
tained in the reactions of naphthalen-2-amine (I) with
dimedone and furan and thiophene derivatives IIa–IIh,
while the yields of pyrrole-containing analogs Vi–Vk
were lower (40–50%).
NMR spectra of IIIb, Va, Vg, and Vi were assigned
with the aid of two-dimensional shift correlation
techniques (COSY-45, NOESY, HSQC, HMBC). All
experimental data were processed using XWIN-NMR
3.5 software package.
The two-dimensional NMR spectra of Va, Vg, and
Vi were analyzed with a view of determining the posi-
tion of the carbonyl group, which is crucial for the
elucidation of the reaction mechanism. The presence of
cross-peaks between the NH proton and C8H2 group in
the HMBC and NOESY spectra convincingly proves
the position of the oxo group on C11. The observed
couplings with quaternary carbon atoms in the HMBC
spectrum were fully consistent with the proposed
structure. The C11 nucleus (δC 193 ppm) displayed
couplings with protons on C12 and C10; the C7a carbon
atom (whose signal was expectedly located at δC 150–
152 ppm) showed cross-peaks with protons on C8 and
C12; and the C11a nucleus (δC 102–106 ppm) was
coupled both with protons on C8 and C12 and with
The structure of compounds IIIa–IIIh and Va–Vk
was confirmed by their elemental compositions and
1H and 13C NMR, IR, and mass spectra. Signals in the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

SYNTHESIS OF 12-HETARYL-9,9-DIMETHYL-7,8,9,10-TETRAHYDRO...
the pseudoequatorial proton on the C10 atom and NH
835
EXPERIMENTAL
proton.
1
The IR spectra were recorded on a Nicolet Protege-
460 spectrometer with Fourier transform from samples
prepared as thin films or KBr pellets. The H and
The H NMR spectra of Schiff bases IIIa–IIIh and
tetrahydrobenzoacridinones Va–Vk are superpositions
of signals from different molecular fragments. The
1H NMR spectra of IIIa–IIIh may be divided into
three parts: (1) seven-spin aromatic proton system of
the naphthalene ring, AB system of the five-membered
heteroaromatic ring, and either AA′BB′ or ABCD sys-
tem (depending on the substitution pattern in the ben-
zene ring). Apart from these parts, the 1H NMR spectra
of Va–Vk contain two AB systems from protons in the
cyclohexane fragment and a singlet from 12-H.
1
13C NMR spectra were measured on a Bruker Avance-
500 spectrometer at 500 and 125 MHz, respectively,
from 2–5% solutions in DMSO-d6; the chemical shifts
were determined relative to tetramethylsilane as in-
ternal standard. The elemental analyses were obtained
on a Vario MICRO Superuser CHNS analyzer, except
for halogen-containing compounds whose elemental
composition was determined by classical micro-
analysis.
According to the two-dimensional NMR correlation
spectra, Schiff bases IIIa–IIIh were formed exclu-
sively as E isomers. In the NOESY spectrum of IIIb
the CH=N proton displayed couplings with 1-H, 3-H,
and 3′-H. Obviously, if the CH=N bond in IIIb had
Z configuration, no couplings with 1-H and 3-H would
be observed because of remoteness of the CH=N
proton from the naphthalene ring. There was no cross-
peak between 1-H and 3′-H in the NOESY spectrum of
IIIb, which also counts in favor of the E configuration;
the corresponding cross peak should be observed for
the Z isomer.
5-Arylfuran-2-carbaldehydes IIa–IIf were syn-
thesized according to a procedure analogous to that
described in [8]. A cold (0–5°C) solution of arenedi-
azonium chloride prepared by diazotization of 0.1 mol
of the corresponding aromatic amine was added drop-
wise under stirring to a solution of 0.1 mol (9.6 g) of
furfural and 1 g of CuCl2·2H2O in 40 mL of acetone.
During the addition, the temperature was maintained in
the range from 20 to 30°C to ensure nitrogen evolution
at a rate of 2–3 bubbles per second. The mixture was
stirred until nitrogen no longer evolved and diluted
with 200 mL of water, and the product was filtered off
or isolated by vacuum distillation (aldehyde IIc) and
recrystallized.
In the IR spectra of IIIa–IIIk stretching vibrations
of the N=CH group give rise to absorption in the
region 1634–1604 cm–1. The IR spectra of IIIa, IIIe,
IIIg, and IIIh contain strong absorption bands at
1356–1343 cm–1 due to stretching vibrations of the
nitro group. Stretching vibrations of the C–F bonds in
IIIc appear at 1151 cm–1. Compounds IIIb and IIIf are
characterized by a medium-intensity band at 489 and
486 cm–1, respectively, which belongs to stretching
vibrations of the C–Br bond. An intense band at
1148 cm–1 in the IR spectrum of IIId was assigned to
symmetric stretching vibrations of the sulfonyl group.
5-(4-Nitrophenyl)furan-2-carbaldehyde (IIa).
Yield 60%, mp 203–204°C; published data: mp 212–
213 [9], 199–200°C [10].
5-(4-Bromophenyl)furan-2-carbaldehyde (IIb).
Yield 44%, mp 151–152°C. Found, %: C 52.43;
H 3.10. C11H7BrO2. Calculated, %: C 52.62; H 2.81.
5-(2-Trifluoromethylphenyl)furan-2-carbalde-
hyde (IIc). Yield 42%, mp 41–42°C. Found, %: C 59.81;
H 2.69. C12H7F3O2. Calculated, %: C 60.01; H 2.94.
In the IR spectra of tetrahydrobenzoacridinones
Va–Vk we observed absorption bands corresponding
to stretching vibrations of free (3440–3400 cm–1) and
associated NH group (3275–3257 cm–1), which is
typical of incomplete association of amines. It is
known that the larger the low-frequency shift of the
latter band and the higher its intensity, the higher the
degree of association [7]. It may be concluded that
tetrahydrobenzoacridinones Va, Vc, Vd, and Vi–Vk
are associated to a greater extent and that compounds
Vb and Vf–Vh are almost unassociated. Stretching vi-
brations of the C=O bond conjugated with the enamine
fragment appeared in the region 1602–1579 cm–1.
4-(5-Formylfuran-2-yl)benzenesulfonamide
(IId). Yield 40%, mp 201–202°C. Found, %: C 52.76;
H 3.70; N 5.45. C11H9NO4S. Calculated, %: C 52.58;
H 3.61; N 5.57.
5-(4-Methoxy-2-nitrophenyl)furan-2-carbalde-
hyde (IIe). Yield 35%, mp 103–104°C. Found, %:
C 58.46; H 3.23; N 5.46. C12H9NO5. Calculated, %:
C 58.30; H 3.67; N 5.67.
5-(2-Bromo-4-methylphenyl)furan-2-carbalde-
hyde (IIf). Yield 36%, mp 80–81°C. Found, %:
C 54.16; H 3.13. C12H9BrO2. Calculated, %: C 54.37;
H 3.42.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

KOZLOV et al.
836
5-Arylthiophene-2-carbaldehydes IIg and IIh
cohol was heated for 40–60 min under reflux. After
cooling, the precipitate was filtered off and recrystal-
lized from alcohol.
(general procedure). The corresponding aromatic
amine, 0.1 mol, was dissolved (if necessary, on heat-
ing) in 60 mL of 20% aqueous HCl. The solution was
cooled to 0–5°C, and a solution of 7 g of sodium nitrite
in 25 mL of water was added dropwise under stirring.
When the reaction was complete, the resulting solution
of arenediazonium salt was filtered and added drop-
wise under stirring to a mixture of 15 mL (12.25 g,
0.11 mol) of thiophene-2-carbaldehyde, 40 mL of
DMSO, and 1.5 g (8.7 mmol) of CuCl2 ·2H2O. The
mixture was stirred at 15–25°C to ensure nitrogen
evolution at a moderate rate. When nitrogen no longer
evolved, the mixture was diluted with 150 mL of
water, and the precipitate was filtered off and recrys-
tallized from ethanol–DMF.
(E)-N-[5-(4-Nitrophenyl)furan-2-ylmethylidene]-
naphthaalen-2-amine (IIIa). Yield 75%, yellow crys-
tals, mp 180°C. IR spectrum, ν, cm–1: 3440, 3117,
2924, 2847, 1685, 1666, 1599, 1514, 1473, 1343,
1329, 1291, 1261, 1105, 1040, 965, 852, 809, 751.
1H NMR spectrum, δ, ppm: 7.25 d (1H, 4′-H), 7.29 d
(1H, 3′-H), 7.35 t (1H, 6-H), 7.49 t (1H, 7-H), 7.51 d.d
(1H, 3-H), 7.62 d (2H, 3″-H, 5″-H), 7.74 d (1H, 1-H),
7.80 d (2H, 2″-H, 6″-H), 7.90–7.93 m (2H, Harom),
7.98 d (1H, 4-H), 8.72 s (1H, CH=N). Found, %:
C 73.73; H 4.16; N 8.11. C21H14N2O3. Calculated, %:
C 73.68; H 4.12; N 8.18.
(E)-N-[5-(4-Bromophenyl)furan-2-ylmethyli-
dene]naphthalen-2-amine (IIIb). Yield 83%, yellow
crystals, mp 144–145°C. IR spectrum, ν, cm–1: 3436,
3085, 3051, 2922, 1630, 1612, 1584, 1472, 1457,
1406, 1375, 1272, 1201, 1163, 1071, 964, 862, 827,
797, 744, 489, 472. 1H NMR spectrum, δ, ppm: 7.31 d
(1H, 4′-H), 7.32 d (1H, 3′-H), 7.47 t (1H, 6-H), 7.52 t
(1H, 7-H), 7.56 d.d (1H, 3-H), 7.70 d (2H, 3″-H,
5″-H), 7.77 d (1H, 1-H), 7.82 d (2H, 2″-H, 6″-H),
7.92 d (1H, 5-H), 7.93 d (1H, 8-H), 7.96 d (1H, 4-H),
8.62 s (1H, CH=N). 13C NMR spectrum, δC, ppm:
154.80 (C5′), 151.81 (C2′), 148.67 (C2), 148.11
(CH=N), 133.70 (C8a), 132.07 (C3′′), 131.61 (C4a),
128.92 (C4), 128.50 (C1′′), 127.88 (C8), 127.58 (C5),
126.48 (C7), 126.22 (C2′′), 125.50 (C6), 121.81 (C4′′),
120.93 (C3), 119.75 (C3′), 118.33 (C1), 109.41 (C4′).
Found, %: C 67.10; H 3.70; Br 21.18; N 3.76.
C21H14BrNO. Calculated, %: C 67.04; H 3.75;
Br 21.24; N 3.72.
5-(4-Nitrophenyl)thiofene-2-carbaldehyde (IIg).
Yield 50%, mp 175–176°C. Found, %: C 56.32;
H 2.96; N 6.12. C11H7NO3S. Calculated, %: C 56.64;
H 3.03; N 6.01.
5-(3-Nitrophenyl)thiophene-2-carbaldehyde
(IIh). Yield 28%, mp 144–145°C [11].
5-Aryl-1-methyl-1H-pyrrole-2-carbaldehydes
IIi–IIk (general procedure). A solution of arenediazo-
nium chloride prepared by diazotization of 0.1 mol of
the corresponding aromatic amine was neutralized,
cooled to 0–5°C, and added dropwise under stirring to
a mixture of 0.1 mol (10.9 g) of 1-methyl-1H-pyrrole-
2-carbaldehyde, 1 g of CuCl2·2H2O, and 4.0 g of mag-
nesium oxide in 40 mL of acetone. The mixture was
stirred at 20–30°C until nitrogen no longer evolved,
200 mL of water was added, and the product was
isolated by vacuum distillation. Aldehyde IIi was
recrystallized from hexane.
(E)-N-[5-(2-Trifluoromethylphenyl)furan-2-yl-
methylidene]naphthalen-2-amine (IIIc). Yield 65%,
yellow crystals, mp 80–82°C. IR spectrum, ν, cm–1:
3430, 3078, 3042, 2918, 1634, 1598, 1523, 1470,
1445, 1413, 1362, 1343, 1267, 1200, 1126, 1150,
1063, 961, 867, 732. 1H NMR spectrum, δ, ppm: 6.79–
6.83 m (2H, 3′-H, 4′-H), 7.30–7.33 m (3H, Harom),
7.52–7.58 m (2H, 7-H, 6-H), 7.79–7.81 m (3H, Harom),
7.89–7.92 m (3H, Harom), 8.64 s (1H, CH=N). Found,
%: N 3.79. C22H14F3NO. Calculated, %: N 3.83.
5-(4-Bromophenyl)-1-methyl-1H-pyrrole-2-car-
baldehyde (IIi). Yield 40%, mp 91–92°C. Found, %:
C 54.34; H 3.69; N 5.52. C12H10BrNO. Calculated, %:
C 54.57; H 3.82; N 5.30.
5-(2-Bromophenyl)-1-methyl-1H-pyrrole-2-car-
baldehyde (IIj). Yield 54%, bp 173–175°C (4 mm).
Found, %: C 54.69; H 4.01; N 5.13. C12H10BrNO. Cal-
culated, %: C 54.57; H 3.82; N 5.30.
5-(2-Chlorophenyl)-1-methyl-1H-pyrrole-2-car-
baldehyde (IIk). Yield 50%, bp 165–170°C (2 mm),
nD20 = 1.6350. Found, %: C 65.75; H 4.26; N 6.17.
C12H10ClNO. Calculated, %: C 65.61; H 4.59; N 6.38.
4-{5-[(E)-(Naphthalen-2-ylimino)methyl]furan-
2-yl}benzenesulfonamide (IIId). Yield 92%, brown
crystals, mp 195–196°C. IR spectrum, ν, cm–1: 3416,
3340, 3240, 3058, 2923, 2853, 1629, 1611, 1600,
1578, 1423, 1324, 1288, 1148, 1094, 1030, 829, 785,
750, 538, 479. 1H NMR spectrum, δ, ppm: 7.50 s (2H,
NH2), 7.18–7.22 m (2H, 3′-H, 4′-H), 7.39–7.43 m (3H,
(E)-N-[5-Arylfuran(thiophen)-2-ylmethylidene]-
naphthaalen-2-amines IIIa–IIIh (general procedure).
A solution of 1.43 g (0.01 mol) of naphthalen-2-amine
(I) and 0.01 mol of aldehyde IIa–IIh in 20 mL of al-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

SYNTHESIS OF 12-HETARYL-9,9-DIMETHYL-7,8,9,10-TETRAHYDRO...
837
Harom), 7.60–7.64 m (2H, 7-H, 6-H), 7.80–7.83 m (3H,
Harom), 7.90–7.95 m (3H, Harom), 8.63 s (1H, CH=N).
Found, %: C 66.93; H 4.28; N 7.42; S 8.43.
C21H16N2O3S. Calculated, %: C 67.00; H 4.28; N 7.44;
S 8.52.
Compounds Va–Vk (general procedure).
a. 5,5-Dimethylcyclohexane-1,3-dione, 1.40 g
(0.01 mol), was added to solution of 0.01 mol of Schiff
base IIIa–IIIh in 30 mL of ethanol, and the mixture
was heated for 2–3 h under reflux. After cooling, the
precipitate was filtered off, washed with diethyl ether,
and recrystallized from ethanol–benzene (1 :2) or
washed with the same solvent mixture.
(E)-N-[5-(4-Methoxy-2-nitrophenyl)furan-2-yl-
methylidene]naphthalen-2-amine (IIIe). Yield 41%,
brown crystals, mp 70–71°C. IR spectrum, ν, cm–1:
3431, 3054, 2963, 2932, 2853, 1611, 1587, 1529,
1479, 1437, 1381, 1356, 1297, 1267, 1226, 1206,
b. A solution of 1.43 g (0.01 mol) of naphthalen-2-
amine (I), 0.01 mol of aldehyde IIa–IIk, and 1.40 g
(0.01 mol) of 5,5-dimethylcyclohexane-1,3-dione in
30 mL of ethanol was heated for 3–4 h under reflux.
After cooling, the product was isolated as described
above in a.
1
1052, 1025, 796, 755. H NMR spectrum, δ, ppm:
3.11 s (3H, OCH3), 6.94 d (1H, 4′-H), 7.29 d (1H,
3′-H), 7.34–7.36 d.d (1H, 5-H), 7.43–7.50 m (3H,
Harom), 7.57 d (1H, 4-H), 7.72 s (1H, 1-H), 7.82 d (1H,
8-H), 7.88–7.93 m (3H, Harom), 8.54 s (1H, CH=N).
Found, %: C 71.00; H 4.38; N 7.49. C22H16N2O4. Cal-
culated, %: C 70.96; H 4.33; N 7.52.
9,9-Dimethyl-12-[5-(4-nitrophenyl)furan-2-yl]-
7,8,9,10-tetrahydrobenzo[a]acridin-11(12H)-one
(Va). Yield 70%, yellow crystals, mp 310–312°C. IR
spectrum, ν, cm–1: 3263, 3192, 3090, 2965, 2939,
2869, 1602, 1582, 1519, 1510, 1491, 1469, 1428,
1390, 1334, 1295, 1260, 1236, 1206, 1144, 1109, 847,
(E)-N-[5-(2-Bromo-4-methylphenyl)furan-2-yl-
methylidene]naphthalen-2-amine (IIIf). Yield 80%,
brown crystals, mp 128–129°C. IR spectrum, ν, cm–1:
3051, 2920, 2854, 1628, 1607, 1584, 1503, 1475,
1461, 1372, 1337, 1270, 1243, 1202, 1163, 1022, 991,
1
825, 815, 784, 750, 591. H NMR spectrum, δ, ppm:
1.00 s and 1.05 s (3H each, CH3), 2.12 d and 2.26 d
(1H each, 10-H), 2.48 d and 2.58 d (1H, 8-H), 5.97 s
(1H, 12-H), 6.12 d (1H, 3′-H), 6.99 d (1H, 4′-H),
7.25 d (1H, 6-H), 7.34 t (1H, 3-H), 7.55 t (1H, 2-H),
7.64 d (2H, 2″-H, 6″-H), 7.75 d (1H, 5-H), 7.79 d (1H,
4-H), 8.16 d (2H, 3″-H, 5″-H), 8.24 d (1H, 1-H), 9.84 s
(1H, NH). 13C NMR spectrum, δC, ppm: 193.11 (CO),
160.57 (C2′), 152.34 (C7a), 148.88 (C5′), 145.40 (C5′′),
136.11 (C1′′), 134.29 (C6a), 131.32 (C12b), 130.28 (C4a),
128.43 (C4), 128.33 (C5), 126.92 (C2), 124.44 (C3′′),
123.87 (C3), 123.11 (C2′′), 122.55 (C1), 117.10 (C6),
113.48 (C12a), 111.34 (C4′), 108.29 (C3′), 102.81 (C11a),
50.26 (C10), 40.18 (C8), 32.23 (C9), 29.80 (C12), 29.20
and 26.46 (CH3). Found, %: C 75.00; H 5.26; N 5.97.
C29H24N2O4. Calculated, %: C 74.98; H 5.21; N 6.03.
1
955, 887, 863, 809, 790, 753. H NMR spectrum, δ,
ppm: 2.21 s (3H, CH3), 6.90 d (1H, 4′-H), 7.20 d (1H,
3′-H), 7.37–7.39 d.d (1H, 5-H), 7.51–7.53 m (3H,
Harom), 7.60 d (1H, 4-H), 7.84 s (1H, 1-H), 7.86 d (1H,
8-H), 7.92–7.96 m (3H, Harom), 8.62 s (1H, CH=N).
Found, %: C 67.80; H 4.09; Br 20.42; N 3.62.
C22H16BrNO. Calculated, %: C 67.71; H 4.13;
Br 20.47; N 3.59.
(E)-N-[5-(4-Nitrophenyl)thiophen-2-ylmethyli-
dene]naphthalen-2-amine (IIIg). Yield 76%, yellow
crystals, mp 195–196°C. IR spectrum, ν, cm–1: 3440,
3051, 2928, 1610, 1587, 1530, 1464, 1350, 1230,
1
1200, 1169, 884, 831, 800, 739, 673, 482. H NMR
spectrum, δ, ppm: 7.45–7.52 m (3H, 3′-H, 4′-H, 3-H),
7.75 m (2H, 7-H, 6-H), 7.88–7.92 m (4H, Harom), 8.01–
8.24 m (4H, Harom), 8.93 s (1H, CH=N). Found, %:
C 70.40; H 4.00; N 7.78; S 9.02. C21H14N2O2S. Cal-
culated, %: C 70.37; H 3.94; N 7.82; S 8.95.
12-[5-(4-Bromophenyl)furan-2-yl]-9,9-dimethyl-
7,8,9,10-tetrahydrobenzo[a]acridin-11(12H)-one
(Vb). Yield 85%, colorless crystals, mp 296°C. IR
spectrum, ν, cm–1: 3427, 3264, 3181, 3090, 2949,
2925, 1593, 1579, 1520, 1499, 1468, 1429, 1400,
(E)-N-[5-(3-Nitrophenyl)thiophen-2-ylmethyli-
dene]naphthalen-2-amine (IIIh). Yield 69%, yellow
crystals, mp 131–132°C. IR spectrum, ν, cm–1: 3443,
3053, 2923, 2854, 1604, 1585, 1526, 1453, 1345,
1288, 1232, 1202, 1165, 890, 863, 825, 802, 744, 732,
1
1266, 1240, 1151, 1072, 823, 781, 746, 593. H NMR
spectrum, δ, ppm: 1.02 s and 1.07 s (3H each, CH3),
2.12 d and 2.28 d (1H each, 10-H), 2.51 d and 2.60 d
(1H each, 8-H), 5.94 s (1H, 12-H), 6.02 d (1H, 4′-H),
6.72 d (1H, 3′-H), 7.26 d (1H, Harom), 7.37–7.40 m
(3H, Harom), 7.52 d (2H, Harom), 7.57 t (1H, Harom),
7.77 d (1H, Harom), 7.82 d (1H, Harom), 8.26 d (1H,
1
678, 476. H NMR spectrum, δ, ppm: 7.38–7.47 m
(3H, 3-H, 3′-H, 4′-H), 7.69–7.73 m (2H, 6-H, 7-H),
7.81–7.87 m (4H, Harom), 8.00–8.19 m (4H, Harom),
8.81 s (1H, HC=N). Found, %: C 70.39; H 3.89;
N 7.86; S 9.01. C21H14N2O2S. Calculated, %: C 70.37;
H 3.94; N 7.82; S 8.95.
Harom), 9.85 s (1H, NH). Found, %: C 70.02; H 4.90;
Br 16.09; N 2.78. C29H24BrNO2. Calculated, %:
C 69.88; H 4.85; Br 16.03; N 2.81.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

KOZLOV et al.
838
9,9-Dimethyl-12-[5-(2-trifluoromethylphenyl)-
3183, 2926, 1599, 1584, 1522, 1501, 1467, 1398,
1382, 1309, 1261, 1239, 1180, 1146, 1124, 1074, 1020,
983, 819, 750, 594. H NMR spectrum, δ, ppm: 0.99 s
and 1.03 s (3H each, CH3), 2.13 d (1H, 10-H), 2.20 s
(3H, 4″-CH3), 2.22 d (1H, 10-H), 2.46 d and 2.53 d
(1H each, 8-H), 5.91 s (1H, 12-H), 6.03 d (1H, 4′-H),
6.81 d (1H, 3′-H), 7.15 d (1H, Harom), 7.24 d (1H,
furan-2-yl]-7,8,9,10-tetrahydrobenzo[a]acridin-
11(12H)-one (Vc). Yield 69%, yellow crystals,
mp 272–273°C. IR spectrum, ν, cm–1: 3427, 3264,
3181, 3090, 2949, 2925, 1593, 1579, 1520, 1499,
1468, 1429, 1400, 1266, 1240, 1151, 1072, 823, 781,
746, 593. 1H NMR spectrum, δ, ppm: 0.95 s and 1.02 s
(3H each, CH3), 2.09 d and 2.22 d (1H each, 10-H),
2.45 d and 2.52 d (1H each, 8-H), 5.94 s (1H, 12-H),
6.14 d (1H, Harom), 6.56 d (1H, Harom), 7.24 d (2H,
arom), 7.32 t (1H, Harom), 7.39 t (1H, Harom), 7.48 d
(1H, Harom), 7.53–7.58 m (1H, Harom), 7.67 d (1H,
arom), 7.73 d (1H, Harom), 7.78 d (1H, Harom), 8.15 d
(1H, Harom), 9.84 s (1H, NH). Found, %: N 2.91.
C30H24F3NO2. Calculated, %: N 2.87.
1
H
H
arom), 7.41–7.48 m (2H, Harom), 7.54–7.59 m (2H,
arom), 7.74 d (1H, Harom), 7.78 d (1H, Harom), 8.22 d
(1H, Harom), 9.81 s (1H, NH). Found, %: C 70.24;
H 5.07; Br 15.66; N 2.69. C30H26BrNO2. Calculated,
%: C 70.32; H 5.11; Br 15.59; N 2.73.
H
H
9,9-Dimethyl-12-[5-(4-nitrophenyl)thiophen-
2-yl]-7,8,9,10-tetrahydrobenzo[a]acridin-11(12H)-
one (Vg). Yield 60%, brown crystals, mp 279–280°C.
IR spectrum, ν, cm–1: 3331, 2954, 2928, 1600, 1581,
1521, 1499, 1467, 1433, 1402, 1328, 1267, 1240,
1153, 1095, 1056, 1021, 832, 815, 800, 745, 618, 544.
1H NMR spectrum, δ, ppm: 0.98 s and 1.03 s (3H each,
CH3), 2.19 d and 2.24 d (1H each, 10-H), 2.43 d and
2.51 d (1H each, 8-H), 6.11 s (1H, 12-H), 6.70 d (1H,
4′-H), 7.25 d (1H, 3′-H), 7.31 d (1H, Harom) 7.35 t (1H,
4-[5-(9,9-Dimethyl-11-oxo-7,8,9,10,11,12-hexahy-
drobenzo[a]acridin-12-yl)furan-2-yl]benzenesulfon-
amide (Vd). Yield 73%, brown crystals, mp 279–
280°C. IR spectrum, ν, cm–1: 3331, 2954, 2928, 1600,
1581, 1521, 1499, 1467, 1433, 1402, 1328, 1267,
1240, 1153, 1095, 1056, 1021, 832, 815, 800, 745,
618, 544. 1H NMR spectrum, δ, ppm: 1.00 s and 1.04 s
(3H each, CH3), 2.12 d and 2.27 d (1H each, 10-H),
2.50 d and 2.56 d (1H each, 8-H), 5.94 s (1H, 12-H),
6.04 d (1H, 4′-H), 6.82 d (1H, 3′-H), 7.25 d (1H,
Harom), 7.30 s (2H, NH2), 7.35 t (1H, Harom), 7.55 d
(1H, Harom), 7.58 d (2H, Harom), 7.60 t (1H, Harom),
7.72–7.76 m (2H, Harom), 7.73 d (1H, Harom), 8.26 d
(1H, Harom), 9.84 s (1H, NH). Found, %: C 69.91;
H 5.22; N 5.58; S 6.70. C29H26N2O4S. Calculated, %:
C 69.86; H 5.26; N 2.87; S 6.43.
H
arom), 7.49 t (1H, Harom), 7.52 t (1H, Harom), 7.79 d
(1H, Harom), 7.88 m (2H, Harom), 8.02 d (1H, Harom),
8.05 d (1H, Harom), 8.21 (1H, Harom), 9.93 s (1H, NH).
Found, %: C 72.52; H 5.07; N 5.78; S 6.70.
C29H24N2O3S. Calculated, %: C 72.48; H 5.03; N 5.83;
S 6.67.
9,9-Dimethyl-12-[5-(3-nitrophenyl)thiophen-2-
yl]-7,8,9,10-tetrahydrobenzo[a]acridin-11(12H)-one
(Vh). Yield 51%, yellow crystals, mp 210–212°C. IR
spectrum, ν, cm–1: 3410, 3251, 3192, 2952, 2929,
1600, 1519, 1508, 1494, 1463, 1430, 1390, 1340,
1265, 1247, 1144, 1109, 1031, 852, 813, 761, 695.
1H NMR spectrum, δ, ppm: 0.96 s and 1.05 s (3H each,
CH3), 2.15 d and 2.28 d (1H each, 10-H), 2.47 d and
2.56 d (1H each, 8-H), 6.15 s (1H, 12-H), 6.66 d (1H,
3′-H), 7.33 d (1H, 6-H), 7.34 d (1H, 4′-H), 7.35 t (1H,
3-H), 7.49 t (1H, 2-H), 7.57 t (1H, 5″-H), 7.84 d (1H,
4-H), 7.84 d (1H, 5-H), 7.86 d (2H, 6″-H), 8.00 d (1H,
4″-H), 8.01 d (1H, 1-H), 8.15 (1H, 2″-H), 10.01 s (1H,
NH). 13C NMR spectrum, δC, ppm: 193.11 (CO),
152.33 (C2′), 151.35 (C7a), 148.29 (C3′′), 138.17 (C5′),
135.49 (C1′′), 134.31 (C6a), 131.21 (C12b), 130.99 (C6′′),
130.52 (C5′′), 130.36 (C4a), 128.53 (C4), 128.46 (C5),
127.10 (C2), 125.19 (C3′), 124.88 (C4′), 123.85 (C3),
122.26 (C1), 121.40 (C4′′), 118.70 (C2′′), 117.10 (C6),
115.07 (C12a), 105.95 (C11a), 50.20 (C10), 40.03 (C8),
32.21 (C9), 31.08 (C12), 29.13 and 26.61 (CH3). Found,
%: C 72.42; H 5.00; N 5.81; S 6.71. C29H24N2O3S.
Calculated, %: C 72.48; H 5.03; N 5.83; S 6.67.
12-[5-(4-Methoxy-2-nitrophenyl)furan-2-yl]-
9,9-dimethyl-7,8,9,10-tetrahydrobenzo[a]acridin-
11(12H)-one (Ve). Yield 62%, yellow crystals,
mp 288–290°C. IR spectrum, ν, cm–1: 3262, 3186,
3082, 2951, 2928, 2868, 1599, 1582, 1536, 1500,
1466, 1386, 1310, 1279, 1262, 1237, 1206, 1147,
1
1024, 822, 800, 788, 750. H NMR spectrum, δ, ppm:
1.00 s and 1.02 s (3H each, CH3), 2.13 d and 2.19 d
(1H each, 10-H), 2.52 d and 2.55 d (1H each, 8-H),
3.76 s (3H, OCH3), 5.87 s (1H, 12-H), 6.09 d (1H,
4′-H), 6.44 d (1H, 3′-H), 7.12 d (1H, Harom), 7.24 d
(1H, Harom), 7.30–7.32 m (2H, Harom), 7.45–7.52 m
(2H, Harom), 7.78 d (1H, Harom), 8.11 d (1H, Harom),
9.79 s (1H, NH). Found, %: C 80.21; H 6.00; N 3.16.
C30H27NO3. Calculated, %: C 80.15; H 6.05; N 3.12.
12-[5-(2-Bromo-4-methylphenyl)furan-2-yl]-
9,9-dimethyl-7,8,9,10-tetrahydrobenzo[a]acridin-
11(12H)-one (Vf). Yield 67%, colorless crystals,
mp 310–312°C. IR spectrum, ν, cm–1: 3435, 3257,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

SYNTHESIS OF 12-HETARYL-9,9-DIMETHYL-7,8,9,10-TETRAHYDRO...
839
12-[5-(4-Bromophenyl)-1-methyl-1H-pyrrol-
2-yl]-9,9-dimethyl-7,8,9,10-tetrahydrobenzo[a]acri-
din-11(12H)-one (Vi). Yield 50%, gray crystals,
mp >320°C. IR spectrum, ν, cm–1: 3430, 3269, 3192,
3077, 2951, 2929, 1600, 1519, 1508, 1494, 1463,
1430, 1390, 1340, 1265, 1247, 1144, 1109, 1031, 852,
tals, mp 289–290°C. IR spectrum, ν, cm–1: 3462, 3275,
3191, 3090, 3063, 2961, 2929, 2872, 1594, 1581,
1520, 1493, 1468, 1450, 1428, 1396, 1383, 1258,
1
1236, 1146, 1036, 812, 744, 694, 581. H NMR spec-
trum, δ, ppm: 0.89 s and 0.99 s (3H each, CH3), 2.07 d
and 2.21 d (1H each, 10-H), 2.39 d and 2.52 d
(1H each, 8-H), 3.69 s (3H, NCH3), 5.47 s (1H, 12-H),
5.69 d (1H, 4′-H), 7.24 d (1H, 3′-H), 7.27–7.31 m (4H,
1
813, 761, 695. H NMR spectrum, δ, ppm: 0.97 s and
1.05 s (3H each, CH3), 2.13 d and 2.25 d (1H each,
10-H), 2.47 d and 2.57 d (1H each, 8-H), 4.01 s (3H,
NCH3), 5.59 d (1H, 3′-H), 5.79 s (1H, 12-H), 5.91 d
(1H, 4′-H), 7.24 d (1H, 2″-H, 6″-H), 7.35 d (1H, 6-H),
7.35 t (1H, 3-H), 7.52 t (1H, 2-H), 7.52 d (1H, 3″-H,
5″-H), 7.77 d (1H, 5-H), 7.82 d (1H, 4-H), 7.94 d (1H,
1-H), 9.91 s (1H, NH). 13C NMR spectrum, δC, ppm:
193.49 (CO), 150.77 (C7a), 141.85 (C2′), 133.86 (C6a),
132.51 (C1′′), 131.26 (C3′′), 131.17 (C12b), 130.61 (C5′),
130.35 (C4a), 129.75 (C2′′), 128.46 (C4), 127.66 (C5),
126.86 (C2), 123.55 (C3), 122.00 (C1), 119.07 (C4′′),
117.22 (C6), 116.53 (C12a), 108.55 (C4′), 107.39 (C3′),
106.83 (C11a), 50.33 (C10), 40.30 (C8), 32.30 (NCH3),
32.25 (C9), 28.92 (CH3), 28.10 (C12), 26.69 (CH3).
Found, %: C 70.20; H 5.37; Br 15.58; N 5.42.
C30H27BrN2O. Calculated, %: C 70.15; H 5.32;
Br 15.62; N 5.48.
H
arom), 7.41–7.45 m (3H, Harom), 7.72 d (1H, Harom),
7.76 t (1H, Harom), 7.87 t (1H, Harom), 9.86 s (1H, NH).
Found, %: C 77.21; H 5.40; Cl 7.52; N 5.92.
C30H27ClN2O. Calculated, %: C 77.16; H 5.83;
Cl 7.59; N 6.00.
REFERENCES
1. Delfourne, E., Roubin, C., and Bastide, J., J. Org.
Chem., 2000, vol. 65, p. 5476.
2. Antonini, J., Polucci, P., Magnano, A., and Martelli, S.,
J. Med. Chem., 2001, vol. 44, p. 3329.
3. Ferlin, M.G., Marzano, C., Chiarelotto, G., Bacci-
chetti, F., and Bordin, F., Eur. J. Med. Chem., 2000,
vol. 35, p. 827.
4. Blache, Y., Benezech, V., Chezal, J.-M., Boule, P.,
Viols, H., Chavignon, O., Teulade, J.-C., and
Chapat, J.-P., Heterocycles, 2000, vol. 53, p. 905.
5. Kozlov, N.G., Bondarev, S.L., Kadutskii, A.P., and Basa-
laeva, L.I., Russ. J. Org. Chem., 2010, vol. 46, p. 202.
6. Kozlov, N.G., Basalaeva, L.I., and Odnoburtsev, B.A.,
12-[5-(2-Bromophenyl)-1-methyl-1H-pyrrol-
2-yl]-9,9-dimethyl-7,8,9,10-tetrahydrobenzo[a]acri-
din-11(12H)-one (Vj). Yield 44%, gray crystals,
mp 283°C. IR spectrum, ν, cm–1: 3440, 3276, 3191,
3089, 2959, 2925, 2889, 1600, 1582, 1519, 1493,
1451, 1427, 1397, 1381, 1257, 1235, 1144, 1113, 822,
Russ. J. Org. Chem., 2010, vol. 46, p. 740.
7. Kazitsyna, L.A. and Kupletskaya, N.B., Primenenie UF,
IK, YaMR i mass spektroskopii v organicheskoi khimii
(Application of UV, IR, NMR, and Mass Spectroscopy
in Organic Chemistry), Moscow: Mosk. Gos. Univ.,
1979, 2nd ed., p. 77.
8. Obushak, N.D., Lesyuk, A.I., Ganushchak, N.I.,
Mel’nik, G.M., and Zavalii, P.Yu., Zh. Org. Khim., 1986,
vol. 22, p. 2331.
1
759, 746, 684, 580. H NMR spectrum, δ, ppm: 0.90 s
and 0.99 s (3H each, CH3), 2.07 d and 2.20 d (1H each,
10-H), 2.45 d and 2.54 d (1H each, 8-H), 3.72 s (3H,
NCH3), 5.45 s (1H, 12-H), 5.70 d (1H, 4′-H), 7.21–
7.41 m (7H, Harom), 7.62 d (1H, Harom), 7.73 d (1H,
Harom), 7.88 d (1H, Harom), 10.07 s (1H, NH). Found,
%: C 70.11; H 5.36; Br 15.65; N 5.51. C30H27BrN2O.
Calculated, %: C 70.15; H 5.32; Br 15.62; N 5.48.
9. Malinowski, S., Roczn. Chem., 1953, vol. 27, p. 54.
10. McClure, M., Glover, B., and McSorley, E., Org. Lett.,
12-[5-(2-Chlorophenyl)-1-methyl-1H-pyrrol-
2-yl]-9,9-dimethyl-7,8,9,10-tetrahydrobenzo[a]acri-
din-11(12H)-one (Vk). Yield 40%, light brown crys-
2001, vol. 3, no. 11, p. 1677.
11. Obushak, N.D., Matiychuk, V.S., and Lytvyn, R.Z.,
Chem. Heterocycl. Compd., 2008, vol. 44, p. 936.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014